Diagram illustrating the cellular and molecular elements involved in the baroreceptor reflex. The baroreceptor reflex is initiated by pressure-induced stretch of baroreceptors located at afferent nerve terminals in the aortic arch and carotid sinuses. The vagus nerve and the glossopharyngeal nerve are two afferent nerves that innervate the aortic arch and carotid sinus. Baroreceptor activation generates afferent nerve impulses that are conveyed to the cardiovascular center in the pons and medulla. This subsequently changes autonomic efferent activity, leading to changes in HR and BP. A number of ion channels including ENaC, ASIC2, TRPC5, and Piezo have previously been considered as molecular substrates of baroreceptors. Lu et al. show that TTN3 is a baroreceptor located at the vagus nerve terminals innervating the aortic arch and is essential for the baroreceptor reflex.